Allergic Asthma Pathogenesis and Antioxidant Therapy

Allergic asthma is a worldwide chronic inflammatory disease characterized by cycles of airway obstruction due to recurrent episodes of respiratory smooth muscle contraction and bronchoconstriction. Public awareness of asthma has increased over the past few decades due to higher prevalence, especially among younger generations. Many research efforts are dedicated to the understanding of this complex disorder and the role of genetic and environmental factors. Emerging evidence from animal studies and clinical trials has identified oxidative stress (OS) as an important factor contributing to asthma pathogenesis. In addition, observational epidemiologic studies suggest a possible correlation between impaired intake of antioxidants and increased prevalence of allergic asthma. The imbalance between antioxidants and oxidants in the respiratory airway due to overproduction of reactive oxygen species (ROS) or overwhelmed antioxidant system indicates a strong association between ROS and asthma. Although physiological levels of ROS are essential for the modulation of cell signaling pathway, excessive ROS production can lead to worsened physiological conditions, including increased airway hyperresponsiveness, epithelial shedding, vascular permeability, mucus secretion, as well as other inflammatory responses through the upregulation of proinflammatory mediators. In particular, the exposure to sources such as allergens, air pollution, and tobacco smoke, not only triggers airway inflammation, but also provides exogenous ROS. Simultaneously, overreacted immune responses exacerbate ROS formation, which furthers the inflammation. Redox therapeutics has become a potential approach in alleviating OS and restoring oxidant-antioxidant balance. However, redox therapeutics is limited by ineffective measurement of lung redox status due to the lack of standard biomarkers of OS and antioxidant capacity. Moreover, the responses to antioxidants are largely dependent on the stage of the disease, genetic susceptibility, and external sources of OS. These aspects also pose a great challenge to the redox therapeutics. The antioxidants, either antioxidant enzymes or non-enzymatic antioxidants, are frequently used in the treatment for multiple diseases, including neurodegenerative, cardiovascular, skin, and liver diseases. Particularly, the intake of antioxidant supplements, such as vitamin C, and dietary changes are proposed to decrease asthma prevalence and enhance asthma control. However, limited data has displayed their beneficial effects on asthma subjects clinically. The exact mechanism by which ROS influence the lung tissue remains unclear. Future studies may be focused on the molecular mechanisms of redox processes as well as the development of treatments in allergic asthma.

In this chapter, we will discuss the specific antioxidants from supplement and diet that are potential agents for the treatment and prevention of asthma. The pathogenesis of allergic asthma and its correlation with inflammation and ROS/OS will be presented. The development of potential biomarkers of OS and effective therapeutic redox intervention will be discussed in this chapter.

Keywords: Airway hyperresponsiveness, allergen, allergic asthma, antioxidant, FENO, inflammation, inhaled corticosteroids, oxidative stress, reactive oxygen species, vitamin.